For more than two decades, our laboratory has been studying technology to develop, manage, and use formal descriptions of biomedical concepts. The result of this work is Protege, a workbench that allows users to edit and apply controlled terminologies, ontologies, and knowledge bases to a wide range of information-management problems. To date, more than 50,000 people have registered as users of the system. Many diverse projects in biomedicine-supported by nearly every institute and center at NIH-have become critically dependent on this software and the knowledge-engineering principles that it supports. This P41 competing renewal application seeks to continue support for Protege, as a biomedical informatics resource that will benefit the system's entire user community. We propose technology research and development to expand the capabilities of the Protege system to meet the current and anticipated needs of the user community. We will re-engineer Protege with a service-oriented architecture that can adapt to the requirements of new ontology languages, large ontology repositories, and cutting-edge ontology-management-services, such as reasoning, alignment, and evolution. We will create support for collaborative ontology development, in the context of both large, centralized projects and open, decentralized efforts. We also will develop advanced support for using ontologies in application software development and as integral parts of software systems. As a biomedical informatics resource, we will expand our collaborative research projects with other Prot[unreadable]g[unreadable] users. We will provide service to the Protege user community through enhanced technical support, user documentation, tutorials, and workshops. These activities will serve to disseminate information about the resource and will aid research and development in many aspects of biomedical informatics both in the United States and internationally.